HE4 tumor marker concentration in neoplastic peritoneal effusion and in peritoneal fluid associated with benign gynecological diseases

BACKGROUND: The aim of our study was to evaluate the behaviour of the human epididymis protein 4 (HE4) in the peritoneal fluid encountered in various female genital diseases. METHODS: We enrolled 139 patients, 40 with ovarian cancer (group I), 82 with benign diseases (group II), and 17 with other malignant neoplasms (group III). The HE4 tumor marker concentrations were determined in serum, in the peritoneal effusion and ovarian cyst/ tumor fluids, CA125 in the serum only. We compared the groups, examined correlations and determined corresponding ROC curves. We evaluated the relationship between the HE4 marker concentration in the peritoneal effusion in the group I, depending on the selected prognostic parameters. RESULTS: The HE4 median value between the study groups did not differ statistically significantly and were as follows: in group I 3322 pmol/L, in the group II 2150 pmol/L and in the group III 627 pmol/L (p = 0.206376 for the groups I and II, p = 0.05929 for the groups I and III and p = 0.0797 for the groups II and III. In group I there were no differences found in the HE4 concentrations in the peritoneal fluid, depending on the stage, grade, the presence of neoplastic cells and the peritoneal dissemination. CONCLUSIONS: The HE4 marker concentrations in the peritoneal fluid are highly irrespective of the pathology observed in the female sexual organ. Therefore, it seems that its determinations in the peritoneal fluid are completely useless in terms of diagnostics. More research is needed on the role of the HE4 marker, especially the place of its formation and possible use in the targeted therapy

Charakterystyka wybranych aspektów klinicznych u kobiet, nosicielek mutacji genu BRCA1 poddanych operacjom profilaktycznym narządu płciowego leczonych uprzednio z powodu raka piersi

Aim: Evaluation of patient age and time of the prophylactic surgery, as well as incidence of genital cancers and precancerous states observed in histopathology of the postoperative material from BRCA1 gene mutation carriers previously treated for breast cancer. Material and methods: 206 carriers of one of the three most common BRCA1 gene mutations (5382insC, C61G and 4153delA) in the Polish population, who were offered the option of prophylactic salpingo-oophorectomy. The study group comprised 85 patients with the diagnosis of breast cancer before gynecological preventive surgery. The study group was further divided into two subgroups for more detailed assessment of the tested variables. The first subgroup included 67 patients with breast cancer (unilateral or bilateral synchronous). The second subgroup included 18 patients with bilateral metachronous (the second diagnosis of breast cancer was at least 12 months after the first breast cancer diagnosis). The control group consisted of 121 patients with no cancerous lesions before preventive gynecologic surgery. The patients undergoing prophylactic treatment had no prior symptoms in female sexual organ and no changes in the diagnostic tests. Results: The patients with a history of breast cancer underwent genetic testing and preventive surgery of the genital tract at a significantly later age than controls (respectively, p = 0.0003, p = 0.0006). The patients with bilateral metachronous breast cancer underwent preventive surgery significantly earlier (p = 0.03). There was a trend indicating a 2.5 times higher risk of developing ovarian cancer among BRCA1 mutation carriers who had already been diagnosed and treated for breast cancer, when compared to women without breast cancer diagnosis. The incidence of other genital cancers and precancerous states in BRCA1 gene mutation carriers with history of breast cancer was not statistically significant as compared to controls. Data on the clinical stage, morphological grade, histological type, age and type of pathology, and the type of BRCA1 gene mutation did not show a statistically significant difference between the groups. Conclusions: Each patient diagnosed with breast cancer should be strongly recommended a genetic test to reduce adverse consequences resulting from postponing the test and, if applicable, the preventive operation until later in life. Preventive surgery should be considered especially in BRCA1 gene mutation carriers previously treated for breast cancer because of the increased risk of ovarian cancer.Cel pracy: Ocena wieku i czasu wykonania operacji profilaktycznej oraz częstości występowania raków i stanów przedrakowych narządu płciowego stwierdzanych w badaniu histopatologicznym materiału pooperacyjnego u pacjentek nosicielek mutacji genu BRCA1 leczonych uprzednio z powodu raka piersi. Materiał i metody: Materiał stanowiło 206 pacjentek nosicielek jednej z trzech najczęstszych mutacji dla populacji polskiej (5382insC, 4153delA i C61G) genu BRCA1 (16), którym przedstawiono jako opcję – zabieg profilaktycznego usunięcie przydatków. U pacjentek wykonano operacje profilaktyczne w okresie od 15.09.1999r. do 31.12.2010r. Były to kolejne nosicielki mutacji pochodzące z województwa zachodniopomorskiego, operowane w Katedrze i Klinice Ginekologii Operacyjnej i Onkologii Ginekologicznej Dorosłych i Dziewcząt PUM w Szczecinie. Wyniki: U pacjentek poddanych zabiegowi profilaktycznemu wcześniej nie stwierdzono jakichkolwiek objawów ze strony narządu płciowego i zmian w badaniach diagnostycznych. Grupę badaną (A) stanowiło 85 pacjentek leczonych przed operacją profilaktyczną z powodu raka piersi. W celu dokładniejszej oceny badanych zmiennych grupę badaną A podzielono dodatkowo na dwie podgrupy: B i C. Do podgrupy B włączono 67 pacjentek z rakiem piersi ( jednej piersi lub obustronnym rakiem - zdiagnozowanym w tym samym czasie). Do podgrupy C włączono 18 pacjentek z obustronnym rakiem piersi zdiagnozowanym w różnym czasie, czas jaki upłynął od pierwszej diagnozy wynosił co najmniej 12 miesięcy). Grupę kontrolną (K) stanowiło 121 pacjentek, u których przed operacją profilaktyczną nie stwierdzono żadnych nowotworów złośliwych. W grupie badanych pacjentek porównywano wiek i czas od podjęcia decyzji dotyczącej zabiegu profilaktycznego do wieku pacjentek i czasu poddania się przez nie operacji. Wnioski: Każdej pacjentce, z rozpoznanym rakiem piersi należy zdecydowanie zaproponować wykonanie badanie genetycznego, aby zmniejszyć niekorzystne tendencje późniejszego zgłaszania się na badania genetyczne i w związku z tym wykonywania operacji profilaktycznej w późniejszym wieku. Wykonanie operacji profilaktycznej szczególnie należy rozważyć u pacjentek, nosicielek mutacji genu BRCA1, leczonych w przeszłości z powodu raka piersi z uwagi na wzrost ryzyka zachorowania na raka jajnika

Expression of selected angiogenesis-related small microRNAs in patients with abnormally increased secretion of glucocorticoids

Introduction: Higher cortisol levels are associated with cardiovascular morbidity and mortality in the elderly, partially resulting from biologic effects of glucocorticoids (GCs) on endothelial cells observed in an experimental setting. These features are replicated in patients with endogenous GC excess (Cushing’s syndrome) or with exogenous hypercortisolism due to excessive pharmacological application of GCs. Both groups present also an increased cardiovascular disease event rate. GCs may also adversely influence recovery after myocardial infarction. Recently it was proposed that microRNAs (miRNAs) — small noncoding RNAs functioning as antisense regulators of gene expression by targeting mRNA — may have a central role in regulating endothelial function through multiple mechanisms. Thus, the purpose of this study was to evaluate the effects of chronic GC excess on the expression of selected endothelium-controlling miRNAs expressed in nucleated cells circulating in peripheral blood (PBNCs) of patients with endogenous hypercortisolism either due to corticotrophin‐independent or corticotrophin‐dependent Cushing’s syndrome (CS). Material and methods: Peripheral blood nuclear cells were collected from 35 healthy subjects and 31 patients with endogenous hypercortisolism as a source of miRNAs. A self-validated individual quantitative RT-PCR study was then performed to evaluate the expression levels of selected miRNAs in PBNCs. Additionally, endothelin-1 (ET-1) expression in peripheral blood was assessed with respect to endothelial dysfunction using Western blotting. Results: The ET-1 expression levels in CS were higher than in controls, confirming endothelial dysfunction in the CS group. Furthermore, miRNA analysis revealed a significantly decreased intracellular expression of selected endothelium-related miRNAs in patients with endogenous hypercortisolism, including miRNA-17-5p, miRNA-126-3p, and miRNA-126-5p, compared to controls. In contrast, two other angiogenic miRNAs, miRNA-150-5p and miRNA-223-3p, were significantly upregulated compared to controls. Conclusions: Cardiovascular events related to hypercortisolism remain a challenging problem in medical practice. This study has demonstrated that the chronic excess of GCs in endogenous CS might induce significant dysregulation of selected miRNAs involved in the control of endothelium biology. However, the lack of knowledge about specific miRNA expression postpones the full understanding of the biological roles of such miRNAs in hypercortisolism. Moreover, dysregulated miRNAs seem to be promising targets for further research, especially to search for potential therapies for several GC-induced cardiovascular complications

The Role of Zinc and Copper in Gynecological Malignancies

Zinc (Zn) and copper (Cu) are essential microelements, which take part in cellular metabolism, feature in enzymatic systems, and regulate enzyme activity. Homeostasis of these micronutrients is tightly regulated by multiple compensatory mechanisms that balance their concentrations including transporters, importers, and metallothioneins. An altered intake of only one of these trace elements may cause an imbalance in their levels and result in their competition for absorption. Relatively low levels of zinc and increased levels of copper may result in an increased level of oxidative stress and impair the antioxidant properties of multiple enzymes. Altered levels of trace elements were discovered in various pathologies including immunological, degenerative, and inflammatory diseases. Moreover, due to the role of Zn and Cu in oxidative stress and chronic inflammation, they were found to influence cancerogenesis. We review the roles of zinc and copper and their mechanisms in tumor growth, metastasis potential, microenvironment remodeling, and drug resistance. We highlight their role as potential biomarkers for cancer diagnosis, treatment, and prognosis, concentrating on their impact on gynecological malignancies

Micro-Focused Ultrasound Therapy in Patients with Urogenital Atrophy and Vaginal Laxity

Vaginal laxity (VL) and genitourinary syndromes of menopause (GSM) create physical, psychological, and functional problem for women and their partners. We aimed to evaluate the efficacy and safety of micro-focused ultrasound (MFU) therapy performed twice in the vaginal canal in a patients with VL and GSM. A total of 20 women with GSM and VL were treated with MFU Ultravera by Hironic. The treatment course consisted of two vaginal applications of MFU at an interval of 6 weeks. The clinical effects of the protocol were evaluated using the Vaginal Laxity Questionnaire (VLQ), the Vaginal Health Index (VHI), and the Female Sexual Function Index (FSFI). The overall values of the vaginal laxity evaluation for the total subject population showed a statistically significant improvement between the baseline and the findings at 3 and 6 months after treatment. The effect of therapy was consistent across all domains of FSFI. It peaked at the 6 week follow-up visit (from 26.5 to 32) and plateaued at 12 weeks and 6 months. There was a significant VHI improvement over time, with the greatest and most significant change between the study entry and 21 days after treatment; the VHI score leveled off up to 3 months after the procedures. MFU therapy, performed twice in the vaginal canal, showed promising efficacy and safety profiles, meriting further investigation

The Role of Iron and Cobalt in Gynecological Diseases

Iron and cobalt are micronutrients that play an important role in the regulation of cellular processes, being part of the centre of catalases, peroxidases, cytochromes and metalloproteins such as hemoglobin and myoglobin (Fe). Cobalt primarily functions as a component of hydroxycobalamin, which is essential for regulating red blood cell production. Maintaining normal levels of cobalt and iron in the human body is important, as a deficiency can lead to anaemia. These elements are also involved in reactions during which oxidative stress occurs and are therefore considered to be a cause of tumor formation. This paper will discuss aspects of the influence of cobalt and iron on mechanisms that may contribute to the growth of gynecological tumors, as well as other obstetric-gynecological disease entities, by altering the conditions of the microenvironment. In addition, the following review also highlights the role of cobalt and iron in the treatment of gynecological tumors

The Role of Iron and Cobalt in Gynecological Diseases

Iron and cobalt are micronutrients that play an important role in the regulation of cellular processes, being part of the centre of catalases, peroxidases, cytochromes and metalloproteins such as hemoglobin and myoglobin (Fe). Cobalt primarily functions as a component of hydroxycobalamin, which is essential for regulating red blood cell production. Maintaining normal levels of cobalt and iron in the human body is important, as a deficiency can lead to anaemia. These elements are also involved in reactions during which oxidative stress occurs and are therefore considered to be a cause of tumor formation. This paper will discuss aspects of the influence of cobalt and iron on mechanisms that may contribute to the growth of gynecological tumors, as well as other obstetric-gynecological disease entities, by altering the conditions of the microenvironment. In addition, the following review also highlights the role of cobalt and iron in the treatment of gynecological tumors

The Role of TIM-3 and LAG-3 in the Microenvironment and Immunotherapy of Ovarian Cancer

Ovarian cancer has the highest mortality rate among gynecologic malignancies. The main treatment options are surgical removal of the tumor and chemotherapy. Cancer treatment has been revolutionized by immunotherapy, which has developed explosively over the past two decades. Clinical anticancer strategies used in immunotherapy include therapies based on the inhibition of PD-1, PD-L1 or CTLA-4. Despite encouraging results, a large proportion of cancer patients are resistant to these therapies or eventually develop resistance. It is important to perform research that will focus on immunotherapy based on other immune checkpoint inhibitors. The aim of the review was to analyze studies considering the expression of TIM-3 and LAG-3 in the ovarian cancer microenvironment and considering immunotherapy for ovarian cancer that includes antibodies directed against TIM-3 and LAG-3. As the data showed, the expression of the described immune checkpoints was shown in different ways. Higher TIM-3 expression was associated with a more advanced tumor stage. Both TIM-3 and LAG-3 were co-expressed with PD-1 in a large proportion of studies. The effect of LAG-3 expression on progression-free survival and/or overall survival is inconclusive and certainly requires further study. Co-expression of immune checkpoints prompts combination therapies using anti-LAG-3 or anti-TIM-3. Research on immune checkpoints, especially TIM-3 and LAG-3, should be further developed

Therapeutic Management of Rare Primary Ovarian Neoplasms: Carcinosarcoma, Leiomyosarcoma, Melanoma and Carcinoid

Carcinosarcoma, leiomyosarcoma, melanoma and carcinoid as primary tumors in the ovary are extremely rare. In this paper, the authors reviewed the literature from 2010 to 2021, based on specific criteria, to analyze the treatment of these rare ovarian neoplasms. We also aimed to verify whether modern therapies have been found in recent years. For this article, 80 papers were finally selected. The vast majority of the articles were clinical case reports. Despite single mentions of new potential pharmacological treatments, surgery (radical or fertility-sparing) is definitely the mainstay of treatment. There are currently no treatment guidelines for these tumors. A review of the literature has revealed the use of various adjuvant treatments. We, therefore, believe that a more detailed understanding of the biology of these tumors is necessary in order to find new target points for treatment. We would like to emphasize the importance of creating an international database of rare ovarian tumors which would make it possible to gather data from various oncological centers and enable further research into these neoplasms

Ocena jakości życia kobiet z chorobą nowotworową leczonych metodą chemioterapii

Celem pracy jest ocena jakości życia kobiet z chorobą nowotworową leczonych chemioterapią, która jest elementem uzupełniającym leczenie operacyjne raka jajnika. Badaniem objęto 134 pacjentki poddawane chemioterapii w Klinice Ginekologii Operacyjnej i Onkologii Ginekologicznej Dorosłych i Dziewcząt Pomorskiego Uniwersytetu Medycznego w Szczecinie. W badaniu wykorzystano kwestionariusz ankiety FACT-O. Pozwala on na ocenę: samopoczucia, wpływu choroby na życie rodzinne i towarzyskie oraz stanu emocjonalnego i funkcjonowania w życiu codziennym. Do realizacji celu wykorzystano analizę korespondencji. W artykule przedstawiono wyniki poszukiwania zależności między kategoriami cech dotyczących jakości życia pacjentek a wybranymi cechami społeczno-demograficznymi i stopniem zaawansowania choroby. Większość badanych kobiet oceniała pozytywnie swój dobrostan fizyczny, społeczny, funkcjonalny i emocjonalny oraz samopoczucie pod kątem odczuwania innych dolegliwości